Mechanism of environmentally driven conformational changes that modulate H-NS DNA-bridging activity

Elife. 2017 Sep 26:6:e27369. doi: 10.7554/eLife.27369.

Abstract

Bacteria frequently need to adapt to altered environmental conditions. Adaptation requires changes in gene expression, often mediated by global regulators of transcription. The nucleoid-associated protein H-NS is a key global regulator in Gram-negative bacteria and is believed to be a crucial player in bacterial chromatin organization via its DNA-bridging activity. H-NS activity in vivo is modulated by physico-chemical factors (osmolarity, pH, temperature) and interaction partners. Mechanistically, it is unclear how functional modulation of H-NS by such factors is achieved. Here, we show that a diverse spectrum of H-NS modulators alter the DNA-bridging activity of H-NS. Changes in monovalent and divalent ion concentrations drive an abrupt switch between a bridging and non-bridging DNA-binding mode. Similarly, synergistic and antagonistic co-regulators modulate the DNA-bridging efficiency. Structural studies suggest a conserved mechanism: H-NS switches between a 'closed' and an 'open', bridging competent, conformation driven by environmental cues and interaction partners.

Keywords: E. coli; H-NS; Hha; YdgT; bacterial chromatin; biophysics; chromosomes; genes; nucleoid; structural biology.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • DNA / metabolism*
  • Escherichia coli Proteins / chemistry*
  • Escherichia coli Proteins / metabolism*
  • Fimbriae Proteins / chemistry*
  • Fimbriae Proteins / metabolism*
  • Molecular Dynamics Simulation
  • Protein Binding
  • Protein Conformation

Substances

  • Escherichia coli Proteins
  • FimG protein, E coli
  • Fimbriae Proteins
  • DNA

Grants and funding

The funders had no role in study design, data collection and interpretation, or the decision to submit the work for publication.